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Harangi et al. HDL structure and function in dyslipidemia

equilibrium and no significant differences were found correlations between the studied parameters and
between the subgroups. According to the results, the age. Therefore, we concluded that age may not
because of the large inter-individual variability, PON1 influence our results in this study. It must be noted
activity measurement alone might not became a that HDL subfraction ratios are derived secondary
useful biomarker for cardiovascular risk prediction in parameters that may include additional error based on
dyslipidemic patients without vascular complications. method of calculation. Data on further HDL functional
assays such as HDL cholesterol efflux assay,
MPO is a leukocyte-derived heme protein that binds measurement of lecithin: cholesterol acyltransferase or
to HDL. As a part of the innate immune host defense platelet-activating factor-acetylhydrolase activity would
system, MPO uses hydrogen peroxide to generate add further information on HDL property.
an array of reactive oxidant and free radical species
such as hypochlorous acid possessing antimicrobial In summary, we found altered HDL function in
effect. However, these reactive species can also foster dyslipidemic patients, characterized by increased
oxidative injury to host molecules as well. Indeed, level of MPO and MPO/PON1, even in patients
MPO catalyzes generation of nitrating oxidants and without clinically detectable symptoms of vascular
promotes both protein modifications and initiates lipid complications. However, PON1 paraoxonase and
peroxidation leading to enhanced atherosclerosis [24] . arylesterase activities were unaltered. There was a
Plasma, serum, and leukocyte MPO levels have been shift towards the smaller HDL subfractions, but these
associated with coronary artery disease [25] ; incident changes were not significant; indicating that the
risk of myocardial infarction, death, and need for importance of alterations in HDL subfractions might
revascularization [26,27] . In a previous study we found not be crucial in patients with dyslipidemia. Our results
significantly elevated MPO levels in overweight highlights the importance of HDL-associated pro- and
hyperlipidemic patients with or without cardiovascular antioxidant enzymes suggesting the possible clinical
complications [28] . In the present study we also found benefit of MPO/PON1 calculation and confirms that
significantly higher MPO levels in dyslipidemic patients quantification of HDL-C level alone provides limited
without any vascular complications compared to data regarding HDL’s cardioprotective effect. Further
healthy subjects. studies on larger patient populations are needed to
identify and characterize the best markers of HDL
Interestingly, both PON1 and MPO interact at the functions.
same site on HDL, reciprocally modulate each
other’s function, influencing the antioxidant and anti- Data on HDL structural and functional properties may
inflammatory function of HDL [11] . Our previous study improve the efficacy of cardiovascular risk prediction
on a similar patient population also highlighted the and development of novel anti-atherogenic treatment
importance of this reciprocal inhibition [29] . Furthermore, strategies in dyslipidemia.
a recent study showed that serum MPO/PON1 ratio
may be a potential indicator of dysfunctional high- DECLARATIONS
density lipoprotein and risk stratification in coronary
artery disease [30] . Therefore, MPO/PON1 ratio was
also calculated and we found significantly higher MPO/ Authors’ contributions
PON1 ratio in our dyslipidemic patients compared to Study design: M. Harangi, G Paragh
controls indicating an increased risk for cardiovascular Development of methodology: I. Seres
complications. Moreover, in line with the results of Collection of data: B. Nádró, M. Harangi
previous studies, significant negative correlation was Analysis and/or interpretation of data: A. Szentpéteri,
found between myeloperoxidase levels and PON1 H. Lőrincz
arylesterase activities that demonstrates the reciprocal Writing (not revising) all or sections of the manuscript:
inhibition between these two HDL-associated M. Harangi
enzymes. Hence, calculation of MPO/PON1 ratio may Manuscript review: G. Paragh, D. Páll
give information about the function of the enzyme Supervision: G. Paragh
complex and characterize HDL function.
Financial support and sponsorship
Some limitations of the study must be noted. The This research was supported by a grant from the
power of the study may be reduced because of the National Research, Development and Innovation (NFKI)
relatively small size of the study population. Age (OTKA 115723) and by the GINOP-2.3.2-15-2016-00062
was significantly different between the patients project. The project is co-financed by the European
and controls, however, we could not find significant Union under the European Regional Development Fund.

172 Vessel Plus ¦ Volume 1 ¦ December 28, 2017